N-[2-(3,5-dimethoxyphenyl)ethyl]acetamide | 36694-92-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[2-(3,5-dimethoxyphenyl)ethyl]acetamide
• CAS: 36694-92-5
• 化学式: C₁₂H₁₇NO₃
• 分子量: 223.272
• InChiKey: IPHAMWZKKMTVTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[2-(3,5-dimethoxyphenyl)ethyl]acetamide 在 三氟甲磺酸 、 三溴化硼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 N-[2-[3,5-dihydroxy-4-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]phenyl]ethyl]acetamide
  参考文献：
  名称：

  Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability

  摘要：

  Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models. Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure. Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability. Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and "drug likeness", while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group. Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations. Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability.

  DOI：

  10.1021/acsmedchemlett.6b00009
• 作为产物：
  描述：

  3,5-dimethoxy-β-nitrostyrene 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 144.08h， 生成 N-[2-(3,5-dimethoxyphenyl)ethyl]acetamide
  参考文献：
  名称：

  Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability

  摘要：

  Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models. Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure. Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability. Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and "drug likeness", while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group. Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations. Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability.

  DOI：

  10.1021/acsmedchemlett.6b00009

文献信息

• [EN] NOVEL DIHYDROPYRIDOISOQUINOLINONES AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVELLES DIHYDROPYRIDOISOQUINOLINONES ET LEURS COMPOSITIONS PHARMACEUTIQUES POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2016169911A1

  公开（公告）日：2016-10-27

  A compound according to Formula (I): wherein R1, LA, CyA, RA, R2, R3, and R4 are as described herein. The present invention relates to novel compounds according to Formula I that antagonize GPR84, a G-protein-coupled receptor that is involved in inflammatory conditions, and methods for the production of these novel compounds, pharmaceutical compositions comprising these compounds, and methods for the prevention and/or treatment of inflammatory conditions, pain, neuroinflammatory conditions, neurodegenerative conditions, infectious diseases, autoimmune diseases, endocrine and/or metabolic diseases, cardiovascular diseases, leukemia, and/or diseases involving impairment of immune cell functions by administering a compound of the invention.

  根据公式（I）的化合物：其中R1、LA、CyA、RA、R2、R3和R4如本文所述。本发明涉及根据公式I的新化合物，这些化合物拮抗GPR84，GPR84是涉及炎症状况的G蛋白偶联受体，以及制备这些新化合物的方法，包括这些化合物的药物组合物，以及通过给予本发明的化合物预防和/或治疗炎症状况、疼痛、神经炎症状况、神经退行性疾病、传染病、自身免疫疾病、内分泌和/或代谢疾病、心血管疾病、白血病和/或通过给予本发明的化合物导致免疫细胞功能受损的疾病的方法。
• Dihydropyridoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders
  申请人：GALAPAGOS NV

  公开号：US10568879B2

  公开（公告）日：2020-02-25

  A compound according to Formula I: wherein R1, LA, CyA, RA, R2, R3, and R4 are as described herein. The present invention relates to novel compounds according to Formula I that antagonize GPR84, a G-protein-coupled receptor that is involved in inflammatory conditions, and methods for the production of these novel compounds, pharmaceutical compositions comprising these compounds, and methods for the prevention and/or treatment of inflammatory conditions, pain, neuroinflammatory conditions, neurodegenerative conditions, infectious diseases, autoimmune diseases, endocrine and/or metabolic diseases, cardiovascular diseases, leukemia, and/or diseases involving impairment of immune cell functions by administering a compound of the invention.

  符合式 I 的化合物： 其中 R1、LA、CyA、RA、R2、R3 和 R4 如本文所述。 本发明涉及根据式 I 可拮抗参与炎症的 G 蛋白偶联受体 GPR84 的新型化合物、生产这些新型化合物的方法、包含这些化合物的药物组合物，以及通过施用本发明化合物预防和/或治疗炎症、疼痛、神经炎症、神经退行性疾病、传染性疾病、自身免疫性疾病、内分泌和/或代谢性疾病、心血管疾病、白血病和/或涉及免疫细胞功能损害的疾病的方法。
• NOVEL DIHYDROPYRIDOISOQUINOLINONES AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS
  申请人：Galapagos NV

  公开号：EP3286191B1

  公开（公告）日：2020-07-29
• Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability
  作者：William A. Kinney、Mark E. McDonnell、Hua Marlon Zhong、Chaomin Liu、Lanyi Yang、Wei Ling、Tao Qian、Yu Chen、Zhijie Cai、Dean Petkanas、Douglas E. Brenneman

  DOI：10.1021/acsmedchemlett.6b00009

  日期：2016.4.14

  Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models. Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure. Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability. Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and "drug likeness", while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group. Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations. Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability.